It is well-established that the amygdala, a forebrain multinuclear structure, plays a crucial role in emotional[unreadable] behaviors such as fear, anxiety, and stress. It has recently been proposed that the amygdala, in particular the[unreadable] central nucleus (CeA), is also involved in the modulation of pain sensation. Evidence from anatomical,[unreadable] behavioral, and physiological studies support the hypothesis that the amygdala serves as a neural pain center[unreadable] that integrates noxious sensory information and emotions. Preliminary results from our lab and others have[unreadable] demonstrated that electrophysiological changes occur in the central nucleus of the amygdala during periods of[unreadable] persistent pain. For this reason, we have been performing studies aimed at elucidating the signaling cascades[unreadable] involved in the modulation of pain sensation by the amygdala. Our preliminary studies indicate that[unreadable] inflammation of one hindpaw induces acute pain in the injected paw, and after a period of several hours, also[unreadable] in the uninjured contralateral paw. Interestingly, the timing of the onset of this contralateral hypersensitivity[unreadable] coincides with the activation of the extracellular signal regulated kinase (ERK) in the right amygdala,[unreadable] specifically in the laterocapsular subdivision of the central nucleus (CeC). Our preliminary data support the[unreadable] hypothesis that ERK activation in the right (but not left) CeC underlies the development of generalized pain[unreadable] hypersensitivity after inflammation. However, there are still a number of unanswered questions regarding the[unreadable] role of amygdala ERK activation in pain modulation. The present application will address some of these issues.[unreadable] In the first aim, we will test whether the right lateralized ERK activation in the CeC is physiologically relevant in[unreadable] multiple pain models. The second aim of the proposal utilizes patch clamp recordings from brain slices to test[unreadable] the hypothesis that ERK activation leads to acute modulation of neuronal excitability and/or synaptic[unreadable] transmission in the CeC. These studies will lay important groundwork for future investigations of the[unreadable] importance of amygdala ERK signaling in pain sensitization.